Thyroid Flashcards
What are follicles lined by?
cuboidal to low columnar follicular cells
What do parafollicular or C cells secrete? What origin ar they?
calcitonin-promotes absorption of calcium by the skeletal system and inhibits reabsorption of bone
Neural crest origin
What is the mechanism of action and function of thyroid hormones?
- Stimulation of protein synthesis
- Up regulation of carbohydrates and lipid catabolism
- Increase in basal metabolic rate
- critical role in the development of brain in fetuses and neonates
Thyrotoxicosis
Hyper metabolic state due to increased circulating levels of thyroid hormones (T4 and T3)
-most commonly caused by hyper functioning of the thyroid gland but can be not associated with hyperthyroidism
Clinical manifestations of hyperthyroidism/ thyrotoxicosis
Excess thyroid hormone and over activity of sympathetic nervous system
- Increased BMR-soft warm flushed skin
- Heat intolerance and excess sweating
- Weight loss despite increased appetite
- Cardiovascular-increased CO, tachy, palpitaitons, cardiomegaly, arrhythmias especially atrial fibrillation is common in the elderly
- Development of low output heart failure
- Neuromuscular-nervousness, emotional lability, insomnia, muscular weakness, fine tremor of the hands
- proximal muscle weakness and decreased muscle mass
- Gastrointestinal: hypermotility, malabsorption
- Wide staring gaze and lid lag
- Thyroid ophthalmopathy (proptosis) only associated with graves
- Stimulates bone resorption and osteoporosis
- THyroid storm-medical emergency
Diagnosis of hyperthyroidism
TSH levels-usually decreased-Most sensitive
Free T4-usually increased
How do you exclude secondary or pituitary associated hyperthyroidism?
TRH stimulation test
- inject TRH
- if normal rise in TSH then it is not secondary hyperthyroidism
What radioactive iodine uptake results indicate Graves, toxic adenoma, or thyroiditis?
graves: diffuse uptake
toxic adenoma: localized
thyroiditis: reduced uptake
What is the most common cause of hypothyroidism?
primary hypothyroidism
-can be accompanied by enlargement of the gland(goiter)
What is the most common worldwide congenital hypothyroidism due to?
iodine deficiency
Cretinism
Hypothyroidism in infants or early childhood
- secondary to iodine deficiency or rarely from inborn errors in metabolism
- impaired development of skeletal muscles and CNS: severity varies to timing of deficiency
- if maternal thyroid hormone deficiency before development of fetal thyroid, mental retardation is sever
- mental retardation, short stature, coarse facial features
Hypothyroidism Myxedema
Adult hypothyroidism
Gradual slowing of mental and physical activity
-fatigue, lethargy, apathy, slowed speech
-cold intolerance and reduced sweating
-overweight and constipation
-periorbital edema, thick coarse skin, enlarged tongue (deposition of glycosaminoglycans)
-reduced cardiac output causes shortness of breath and decreased exercise capacity
-promotes an atherogenic profile (increased cholesterol)-adverse cardiovascular mortalities
What lab values do you find in hypothyroidism?
Decreased T4
TSH levels-most sensitive for hypothyroidism
Primary-Increased TSH
Secondary-Decreased/normal TSH
Thyroiditis
types with Pain and No pain
- Inflammation with pain, sometimes severe
- Infectious thyroiditis
- subacute granulomatous thyroiditis (De quervain thyroiditis) - Relatively little pain
- Subacute lymphocytic thyroiditis
- Riedel’s thyroiditis
- Hashimoto’s thyroiditis
Hashimoto Thyroiditis
most common hypothyroidism in non-iodine deficient areas
- autoimmune destruction of thyroid gland
- 45-65
- major cause of non endemic goiter in pediatric age group
- strong genetic component
What are the three mechanisms of breakdown in self tolerance and induction of thyroid autoimmunity in Hash?
- T cell mediated cytotoxicity-CD8
- Thyrocyte injury-CD4-INF gamma-macrophages
- Antibody-dependent cell mediated cytotoxicity
What antibodies are seen in hashimoto thyroiditis?
- Thyroglobulin and thyroid peroxidase (TPO)!!!
- TSH receptor
- Iodine receptor
Hashimoto thyroiditis
Gross
Histology
Gross Diffusely enlarged gland Intact Capsule Well demarcated Pale, yellow, tan and somewhat nodular and firm
Histology:
- Thyroid follicles lined by Hurthle cells/oncocytes
- have abundant granular pink cytoplasm (numerous mitochondria) - formation of germinal centers
- Thyroid parenchyma infiltrated by mononuclear inflammatory cells
- blue lymphocytes
- pink cells forming a follicle with colloid in the middle-residual follicular cells
Clinical course Hashimoto Thyroiditis
- transient hyperthyroidism due to disruption of thyroid follicles with release of thyroid hormones (hashitoxicosis)
- gradual hypothyroidism
- increased risk of developing other autoimmune
- increased risk of developing Non Hodgkin B cell lymphoma
Subacute/Granulomatous (de quervain) thyroiditis
40-50 years of age
- viral or post-viral inflammatory response
- viral antigens or virus induced host tissue damage stimulates formation of cytotoxic T cells which then damage the thyroid follicular cells (process is self limited)
- Most Common cause of thyroid pain
- variable enlargement of thyroid
- history of upper respiratory infection
- transient hyperthyroidism–hypothyroidism–euthyroid
- hyperthyroid phase: T3, T4, decreased TSH, radioactive iodine is diminished
- recovery and normal thyroid function in 6-8 weeks
Subacute/Granulomatous (de quervain) thyroiditis
histology
- unilateral or bilateral enlarged firm with intact capsule
- changes are patchy
3.
early stage-disruption of follicles with collections of neutrophils forming microabscesses
later stage-aggregates of lymphocytes, plasma cells and activated macrophages around damaged thyroid follicles
-multinucleated giant cells of enclosed fragments of colloid - eventually chronic inflammation and fibrosis
Riedel thyroiditis
rare disorder of unknown etiology
- extensive fibrosis involving the thyroid and contiguous neck structures
- hard and fixed mass-clinically simulating cancer**
- may be associated with idiopathic fibrosis at other sites like retroperitoneum
- presence of circulating antibodies- autoimmune etiology
Graves Disease
Most common cause of hyperthyroidism
- Hyperthyroidism due to diffuse hyperfunctional enlargement of thyroid
- infiltrative opthalmo exophthalmo-accumulation of loose connective tissue behind eyeballs-weak extraocular muscles
- infiltrative dermopathy pretibial myxedema (present in minority of patients)
- 20-40 yrs
- 30-40% concordance in monozygotic twins as compared to 5% in di
What are the autoantibodies seen in graves disease
- Thyroid stimulating immunoglobulin (TSI)-binds to TSH receptor and mimics its actions (specific for graves)
- Thyroid growth stimulating immunoglobulin-cause(TGI) proliferation of follicular epithelium
- TSH-binding inhibitor immunoglobulin (TBII)
What does graves look like grossly and histologically
Gross
symmetrically enlarged glands
weigh may be >80 g
soft meaty appearance of the parenchyma
Histological:
Crowded and tall follicular cells
Formation of small papillae filling the lumen of the follicles
Papillae do NOT contain fibrovascular cords
Pale colloid with scalloped margins
-lymphoid infiltrate with germinal centers common
What lab findings do you see with graves disease?
Increased serum levels of thyroid hormones
Decreased TSH
Increased radioactive iodine uptake with diffuse uptake on radioiodine scans
What are the treatments to graves disease?
- Beta Blockers- symptomatic treatment of increased adrenergic tone (tachy, palp, tremulousness, anxiety)
- Propylthiouracil: decreased thyroid hormone synthesis
- radioiodine ablation
- surgery
Diffuse/ Nontoxic simple goiter
Gross
HIsto
CLinical
Enlargement of the entire glad without producing nodularity
Diffuse symmetric enlargement
Gross
100-150 gm
cut surface-brown, glassy and translucent
Histologically:
2 phases
1. hyperplastic phage-enlarged thyroid gland with crowded follicular cells
2. colloid involution - some follicles are distended and some are small
-entire gland shows flattened epithelium and follicles filled with colloid
Clinical course
- vast majority euthyroid
- mass effect-large thyroid my press on trachea, esophagus and cosmetic disfigurement
- Normal T4 and T3
- Elevated TSH or in the upper limit of normal
Multinodular Goiter
Gross
Histology
Clinical
Asymmetric enlargement with numerous nodules
- evolvement from diffuse due to repeated episodes of hyperplasia and involution
- older adults
- both polyclonal and monoclonal nodules occur within the same gland
- toxic or non toxic
Gross Asymmetric multilobulated 200 gm irregular nodules containing gelatinous colloid foci of fibrosis and calcification
Histology
Colloid rich follicles lined by flattened inactive epithelium
-areas of follicular hyperplasia DO NOT have a prominent capsule between the hyperplastic nodule and adjacent parenchyma
Multinodular Goiter clinical features? How do you tell if the mass is benign or malignant
- Mass effect with disfigurement or compression
- most patients euthyroid
-minority develop toxic due to development of -
autonomous nodule (plummer’s syndrome)
risk of malignancy
Nodules more likely to be neoplastic in:
90% 20 year survival More likely to neoplastic: -single nodule -young patients -male patients -nonfunctioning "cold" nodule -history of radiation to the head the neck
Follicular Adenoma
Mutation
Gross
Histology
Discrete solitary masses derived from follicular epithelium
Mutation:
RAS or PAX8-PPARG fusion gene
-similar to mutations seen in follicular carcinomas
Gross:
solitary, ENCAPSULATED, spherical mass
-well demarcated, 3cm
-gray-white to red brown mass
-may have areas of hemorrhage, necrosis or calcification
Histology:
neoplastic cells arranged in closely packed follicles
-well defined intact capsule (distinguish from hyperplastic nodules of multinodular goiter)
-uniform small follicles
hurthle cell/oxyphilic/oncocytic adenoma
Follicular Adenoma
Clinical features
- Capsule well defined and intact
- NEED ENTIRE NODULE FOR DIAGNOSIS ***
Painless asymptomatic mass cold on radioactive iodine scan rarely functioning toxic adenoma treatment lobectomy excellent prognosis-do not recur or metastasize
Are males or females more likely to get carcinomas of the thyroid in middle adulthood, what about in childhood and late adult life? What type of carcinoma is most common?
> F early middle adult
M=F childhood and late adult life
Papillary carcinoma
Papillary Carcinoma
commonly 25-50yrs
majority associated with radiation exposure
gross: solitary or multifocal lesion -may be well circumscribed and encapsulated or may be ill defined and infiltrative -papillary structures -foci of fibrosis and calcification
Histology:
Branching papillae with fibrovascular cores lined by multiple layers of cuboidal to columnar epithelium
**Diagnosis based on nuclear features
-longitudinal nuclear grooves
-ground glass or orphan annie eyed nuclei
-psammoma bodies-calcified lamellar concretions usually seen in the cores of the papillae
Variants of Papillary carcinoma
- Follicular variant-based on nuclear features-frequently encapsulated, lower incidence of lymph node and extrathyroidal metastasis and favorable prognosis (no papillae seen)
- Tall variant-tall columnar cells with intense eosinophilic cytoplasm lining the papillary structures, aggressive behavior
- Diffuse sclerosis-younger individuals including kids
- Papillary microcarcinomas-less than 1cm
Papillary Carcinoma clinical features
- May be asymptomatic nodule or lymph node metastasis
- cold
Diagnose:
diagnosed by fine needle aspiration cytology
Treat:
Total thyroidectomy with excision of abnormal appearing lymph nodes
Good prognosis>95% ten-year survival
prognosis dependent on: >40 less favorable, extrathyroid extension and distant metastasis (stage), isolated cervical lymph node met does not have effect on prognosis
Papillary carcinoma genetic events
- Rearrangement of RET
10q11 with RET/PTC translocation 20-40% - Paracentric inversions or translocations of NTRK1 5-10%
- BRAF gene-adverse prognostic factors 33-50%
Follicular Carcinoma
Second most common thyroid cancer
older age 40-60
Higher incidence in iodine deficient area
-minimally invasive or widely invasive
Gross:
-single well circumscribed nodule largely replacing almost the entire lobe
-nodule has light tan appearance and contain foci of hemorrhage
(may be difficult to distinguish from follicular adenomas grossly)
-may extend beyond capsule to involve adjacent neck structures
Histology:
lacks typical nuclear features of papillary carcinoma
-vascular invasion and/or capsular invasion
Follicular Carcinoma clinical course/genetics
- Slowly growing painless nodule
- cold
- hematogenous met to bone, lung, liver
Treatment:
total thyroidectomy with radioactive iodine
Prognosis dependent on metastasis
Genetics:
1/3 to 1/2 PI3K/AKT pathway
1/3 to 1/2 have translocation (2;3)(q13;p25) resulting in PAX8/PPARG fusion product
Medullary Carcinoma
Neuroendocrine neoplasm derived from the parafollicular or C cells
- may secrete calcitonin or ACTH or VIP
- 70 % sporadic (single), 30% familial or associated with MEN2A or 2B (multiple)
- MEN: first decade
- Familial or sporadic: 4 or 5th decade
Gross:
solid grey tan tumor with NO well defined capsule with infiltration of adjacent thyroid parenchyma
-larger lesions with foci of hemorrhage and necrosis
Histological:
polygonal to spindle shaped cells forming nests, trabeculae and follicles
AMYLOID deposits from calcitonin
Medullary carcinoma clinical course
- May be mass or asymptomatic
- may present with paraneoplastic syndrome VIP (diarrhea) and ACTH (cushing)
- MEN2B more aggressive
- hypocalcemia not prominent despite calcitonin
Treatment
total thyroidectomy
MEN-3 with RET mutation are offered prophylactic thyroidectomy as early as possible
Anaplastic carcinoma
undifferentiated tumors accounting for 5%
65 years old
mortality approaches 100% with most patients dying in less than 1 year
histology: highly anaplastic cells, spindles, giant cells
- foci or papillary differentiation may suggest their origin from better differentiated tumor
Clinically:
presents as rapidly enlarging bulky mass
-usually spread
-dyspnea, dysphagia, hoarseness and cough de to compression of neck structures
no effective therapy
Genetic: inactivation of p53 or activating mutations of beta catenin
Thyroglossal duct/cyst
incomplete atrophy o f the duct
- midline cyst or anterior mass
- lined by benign epithelium with normal thyroid and lymphocytes in the wall
- infection with risk of abscess formation
